Atypical hairy cell leukemia with multiple bone lesions

Atypical hairy cell leukemia with multiple bone lesions
Authors of the case:
MD Consultant Pathologist Ugnius Mickys; Resident doctor Gintarė Ražanskienė
A patient was a 68-year-old male with no current complaints and a one-year-prior history of well-differentiated prostate adenocarcinoma. During a routine checkup, he was found to have an elevated prostate specific antigen (PSA) up to 94 μg/l. Magnetic resonance imaging (MRI) scan of the pelvis showed multiple hyperintense bone lesions on T2-weighted sequences. Bone scan demonstrated no abnormal radiotracer accumulation.  His complete blood count was within normal range except for mild monocytosis (1 x109/L). Serum immunofixation showed IgA/lambda monoclone. With the suspicion of possible multiple myeloma, bone marrow (BM) aspiration and trephine biopsy was performed.  
Trephine biopsy from iliac crest demonstrated heterogeneous cellularity up to 70% with distorted architecture and a fibrotic nodular infiltrate near periosteum, constituting 5% of the marrow cellularity (Fig.1).  On H&E staining the infiltrate was composed of medium caliber lymphocytes with irregular and slightly spindly nuclei (due to the stromal fibrosis) (Fig.2).  The infiltrate was strongly positive for CD20, CD103, DBA.44 and, interestingly, CD10 (Fig.3). It also exhibited weak expression of CD123 and CD25 (Fig.4) and was negative for Cyclin D1, Annexin A1, CD23, CD5, TdT and Bcl6. 
Moreover, scattered interstitial infiltrate of monotypic plasma cells (CD138, Ig Lambda, IgA and CD56 positive) was observed (5% of the BM).
The conclusion in the report, regarding the infiltrate was only descriptive in nature, while no definitive diagnosis could be made at the time, due to the atypical pattern and “abortive” immunophenotype.
In order to finally unveil the nature of the lesions, a biopsy from one of them in the ischium was performed. At medium power, H&E staining trephine biopsy exhibited compact solid infiltrate of medium-sized cells with monotonous appearance (Fig.5). The cells had moderate to abundant amount of clear cytoplasm, which created an impression of the characteristic “fried-egg” appearance. The nuclei were irregularly oriented and exhibited polymorphous shape – most commonly oval or round, but some were indented and reniform (Fig.6). The cells were diffusively surrounded by reticular fibers rich stroma (Fig.7).
Immunohistochemical profile differed from the one seen earlier in lymphoid aggregates of the BM. This time the infiltrate was strongly positive for not only CD20, CD103, DBA.44 but also for CD123, CD25, CD11c, Annexin A1. Furthermore, it exhibited characteristic heterogeneous expression of Cyclin D1 (Fig.8) and strong positivity for BRAF (Fig.9) staining. Interestingly, not only bright expression of CD10 was observed but also a heterogeneous expression of Bcl6 in up to 30% of cells (Fig.10).
Due to a characteristic morphology and positive pathognomonic immunomarkers, a diagnosis of hairy cell leukemia was made.
In order to evaluate the extent of the disease, positron emission tomography - computed tomography (PET/CT) was performed. PET/CT scan showed increased FDG uptake in right scapula, 4th rib, corpus of L2 vertebra, multiple sites of pelvic bones, acetabulum and both femurs (Fig.11).
Despite multiple bone lesions, patient reported no constitutional symptoms, exhibited no cytopenia, lymphocytosis or splenomegaly. Therefore, no specific treatment was required. Instead, watch-and-wait approach was chosen.
Hairy cell leukemia (HCL) is a mature B-cell neoplasm that involves primarily blood, bone marrow and splenic red pulp. It represents approximately 2% of adult leukemias and affects predominantly middle-aged men, with male-to-female ratio 4:1.
The unusual name of this disease arose from its odd-looking cells with characteristic circumferential cytoplasmic hairlike projections, seen in blood or BM aspirate smears.
At the beginning of disease BM demonstrate interstitial infiltration pattern (more subtle and infiltrating rather than ‘‘pushing’’ as seen in most of other lymphoproliferative disorders) which, as disease progresses, becomes diffuse.  The infiltrate exhibits typical “fried-egg” appearance, due to abundant clear cytoplasm, which gives the impression of loosely distributed cells, in contrast to other chronic lymphoproliferative disorders, such as CLL and lymphoplasmacytic lymphoma.
The typical HCL immunophenotype includes positivity for pan B-cell markers and more patognomonic markers, such as CD103, CD11c, CD123, CD25, Annexin A1, DBA.44. A heterogeneous positivity for Cyclin D1 is also a very specific finding. Aberrant immunophenotype occur in up to 1/3 of cases. One of the most commonly described aberration is CD10 positivity, seen in about 10% of HCL.  Jasionowski et al. in 2003 reported 11 cases with aberrant expression of CD10 in otherwise typical HCL. Although the cell of origin for HCL is generally believed to be a post–germinal center B cell, the authors hypothesized about possible origin from germinal center due to CD10 expression. Because of the lack of Bcl6 expression in all 11 cases they rejected the idea. Interestingly, the current case demonstrates not only bright CD10 positivity but also heterogeneous Bcl6 positivity.
BRAF V600E mutation occurs in the majority of HCL cases and is a unique feature of HCL amongst other B lymphoproliferative disorders and useful diagnostic tool.
Skeletal involvement is an unusual complication of HCL and in some rare cases, the first sign of manifestation.  Only a bit over 20 cases of HCL with bone lesions have been reported, couple of them exhibiting isolated bone involvement. Most of the lesions occur in proximal femur, pelvic bones and vertebrae. Bone lesions are usually osteolytic but mixed pattern (osteosclerotic and osteolytic) or only marrow-based lesion (as demonstrated in current case) may also be seen.
In contrast to hairy cell leukemia variant (HCL-v), the prognosis of atypical HCL cases with aberrant immunophenotype, unusual morphology and/or clinical presentation does not differ from classical HCL. Hence, the awareness of possible unconventional presentation of HCL is necessary for correct diagnose and appropriate management of this disease.
  1. Sharpe RW, Bethel KJ. Hairy cell leukemia: diagnostic pathology. Hematol Oncol Clin North Am. 2006; 20:1023–1049.
  2. Lemež P, Kačirkova P. Variations of hairy cell nuclei shapes with regard to ring-shaped nuclei simulating dysplastic neutrophilic granulocytes and review of the literature. Int J Lab Hematol. 2014 Oct;36(5):580-6.
  3. Wotherspoon A, Attygalle A, Mendes LS. Bone marrow and splenic histology in hairy cell leukaemia. Best Pract Res Clin Haematol. 2015;28(4):200–207.
  4. Jasionowski TM, Hartung L, Greenwood JH, Perkins SL, Bahler DW. Analysis of CD10+ Hairy Cell Leukemia. Am J Clin Pathol. 2003; 120:228–35.
  5. Gray MT, Rutherford MN, Bonin DM, Patterson B, Lopez PG. Hairy-cell leukemia presenting as lytic bone lesions. J Clin Oncol. 2013 Sep 1;31(25):e410-2.
  6. Pemmaraju N, Gill J, Krause JR. Hairy cell leukemia presenting with a lytic bone lesion. Proc (Bayl Univ Med Cent). 2015;28(1):65–66.
  7. Yonal‐Hindilerden I, Hindilerden F, Bulut‐Dereli S, Yildiz E, Dogan IO, Nalcaci M. Hairy cell leukemia presenting with isolated skeletal involvement successfully treated by radiation therapy and cladribine: a case report and review of the literature. Case Rep Hematol. 2015;2015:803921.

Elaine Jaffe, Daniel A. Arber, Elias Campo, Nancy Lee Harris, Leticia Quintanilla-Fend. (2016). Hematopathology (2nd ed.)